PROJECT SUMMARY The long-term goal of this research is to address two important health disparities faced by Mexican Americans suffering from Alzheimer's disease (AD) and mild cognitive impairment (MCI): (1) younger age of onset and (2) decreased access to early detection and treatment. AD is the most common form of neurodegenerative dementia and the 5th leading cause of death for those over 65 (8th leading cause of death for U.S. Hispanics). AD has an annual health care cost that is greater than that of cardiovascular disease (CVD) and cancer. While death rates from CVD and cancer have declined in recent decades, death rates have steadily increased for AD. The Mexican American elderly population is among the fastest growing segments of the population; however, little research on MCI and AD has been conducted among this underserved group. Here we will leverage our ongoing Health & Aging Brain among Latino Elders (HABLE) study to identify different pathways for MCI and AD among Mexican Americans, define subtle neuroanatomical and blood-based biomarker changes that are related to future risk of MCI and AD as well as provide evidence to support the utility of our AD blood-based detection tool that can be implemented in primary care settings. The current research team consists of leading experts in Mexican American cognitive aging, the epidemiology of MCI and AD as well as biomarkers of MCI and AD (neuroimaging and blood-based). The project will leverage a substantial existing infrastructure and HABLE cohort to address the two health disparities outlined above through the following specific aims: Specific Aim 1 - Examine the impact of higher rates of metabolic burden and depressive symptomatology on MCI and AD among community-dwelling Mexican Americans; Specific Aim 2 - Examine neuroimaging and blood-based biomarkers associated with MCI and AD among Mexican Americans; and Specific Aim 3: Validate our blood-based AD screening tool as the first-step in a multi-stage diagnostic process among Mexican Americans. The current project will address significant health disparities faced by Mexican American elders suffering from and at risk for MCI and AD. The identification of novel pathways related to disproportionate burden of diabetes and depression can lead to novel ethnic-specific interventions. The identification of a blood-based screening tool for AD will provide primary care providers a way of meeting the needs of a rapidly growing elderly Mexican American population.